Inflammatory Bowel Disease and Colorectal Cancer

The reasons for IBD-associated colorectal cancer are not known. For the past decade, the incidence of CRC has been decreasing in the Western World, but in Asian countries, it has been on the rise. The incidence of IBD in these countries is also on the rise, suggesting the two may be linked.

CRC accounts for 1% to 2% of all cancers and is a serious complication of IBD that accounts for around 15% of IBD deaths. The risk of CRC remains in periods of IBD remission.

What is colorectal cancer?

Colorectal cancer is cancer which originates in the colon or the rectum. Symptoms include:

Changes in one’s normal bowel movements

Blood in stool

Bleeding from the rectum

It can begin in the large intestine (colon) or the rectum. There are a number of treatment options for colorectal cancer, including surgery, radiotherapy, or chemotherapy. A combination of these treatments can also be used. The following risk factors are associated with colorectal cancer:

IBD is characterized by the following symptoms:

The range and severity of symptoms may vary depending on where the inflammation occurs. People living with IBD often experience periods of remission in between periods of active illness.

Poor diet and stress were previously thought to be among the immediate causes of IBD. However, it is now believed that while diet and stress may aggravate or worsen IBD, they are not causative factors.

Risk factors for IBD include:

Age

Race and ethnicity

Family history

Smoking

Living location

Nonsteroidal anti-inflammatory medications

Causes of CRC in IBD

Although it doesn’t provide a full explanation, there is increasing interest in the potential for IBD-associated CRC to be caused by genetic alterations. Genetic causes of CRC are different for sporadic versus IBD-associated CRC.

Changes in DNA methylation and microsatellite instability are often detected in the early stages of CRC-associated with ulcerative colitis, and loss of heterozygosity (loss of heterozygosity; where one of the two gene copies in a cell is altered) is common.

An association between a common gene variant (the G308A TNF-α polymorphism) and UC-associated CRC has also recently been made, which reinforces the connection between chronic inflammation and CRC pathogenesis.

There is also evidence to suggest that certain cytokines released by epithelial and immune cells are involved in the pathogenesis of IBD-associated neoplasia.

Tumour growth is promoted by TNF-α and IL-6-induced signalling, and two protein complexes, cyclooxygenase-2 (COX-2) and nuclear factor kappaB (NF-кB), are both involved in the inflammatory process and provide a connection between inflammation and cancer.

Risk factors

The following factors increase the risk of developing IBD-associated CRC:

Family history and the severity of inflammation are also recognised risk factors.

Family history of CRC

Those with a family history of sporadic CRC double the risk of developing CRC compared with patients with no family history of CRC. Studies have shown that people with a first-degree relative with CRC before the age of 50 also had a higher risk of CRC.

Severity of inflammation

Inflammation is believed to promote carcinogenesis, but studies investigating the correlation between increased severity of chronic inflammation and CRC are lacking.

While the pathogenesis of IBD-associated CRC is not fully understood, there are similarities with sporadic colorectal cancer, for instance, CRC in both instances are due to sequential episodes of genomic alteration.

Other factors involved in the pathogenesis of IBD-associated CRC are immune responses to mucosal inflammatory mediators, oxidative stress and intestinal microbiota.

Decreasing the risk of CRC

There are a number of methods for decreasing the risk of CRC, including:

Scheduling regular check-ups with a gastroenterologist

Exercise

Maintaining a healthy diet

Remaining on medications regardless of remission periods

Taking medications to control the inflammation of IBD

Diagnosis

As with many cancers, early diagnosis is key in decreasing the risk of CRC. Options for this include colonoscopic surveillance and treating precancerous lesions. However, evidence for the effectiveness of preventative surveillance methods are yet to be definitively proved.

Treatment

Ongoing inflammation of the colon is thought to be associated with the development of CRC. Anti-inflammatory agents such as 5-aminosalicylate compounds (5-ASAs) and immune modulators have been considered for preventative treatments.

Lois is a freelance copywriter based in the UK. She graduated from the University of Sussex with a BA in Media Practice, having specialized in screenwriting. She maintains a focus on anxiety disorders and depression and aims to explore other areas of mental health including dissociative disorders such as maladaptive daydreaming.

Comments

Very interesting article! I am an identical twin and was Diagnosed with Crohn's Disease as well as Stage 3 Colorectal Cancer (as a result of being misdiagnosed with IBD for ten years). My son was also diagnosed with Crohn’s at 9 years of age. We are very curious what factors contributed to my diagnosis (we have IBD in the family) as my identical twin is healthy.

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